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- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 3. |
- Bernsel, Andreas, et al.
(author)
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Prediction of membrane-protein topology from first principles
- 2008
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:20, s. 7177-7181
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Journal article (peer-reviewed)abstract
- The current best membrane-protein topology-prediction methods are typically based on sequence statistics and contain hundreds of parameters that are optimized on known topologies of membrane proteins. However, because the insertion of transmembrane helices into the membrane is the outcome of molecular interactions among protein, lipids and water, it should be possible to predict topology by methods based directly on physical data, as proposed >20 years ago by Kyte and Doolittle. Here, we present two simple topology-prediction methods using a recently published experimental scale of position-specific amino acid contributions to the free energy of membrane insertion that perform on a par with the current best statistics-based topology predictors. This result suggests that prediction of membrane-protein topology and structure directly from first principles is an attainable goal, given the recently improved understanding of peptide recognition by the translocon.
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- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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- Falk, Erik, 1973-
(author)
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Subject and History in Selected Works by Abdulrazak Gurnah, Yvonne Vera, and David Dabydeen
- 2007
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Doctoral thesis (other academic/artistic)abstract
- This study is concerned with subject formation in the fiction of contemporary postcolonial authors Abdulrazak Gurnah, Yvonne Vera, and David Dabydeen. In contextualised readings of a total of nine works – Gurnah’s Admiring Silence (1996), By the Sea (2001), and Desertion (2005); Vera’s Without a Name (1996), Butterfly Burning (1998), and The Stone Virgins (2002); Dabydeen’s Disappearance (1993), Turner (1994), and A Harlot’s Progress (1999) – it explores thematic and formal aspects of the subject’s constitution in the texts. Investigating the representation of material and discursive traces that constitute the individual, this study has a double aim. First, it describes the particular historical formations that mould the individual in the different texts. Second, it investigates the tactics used to imaginatively upset these formations in order to present new and more enabling modes of being.Gurnah’s fiction depicts the intricate meshwork of social codes, emotions, and narratives that shape subjectivity in a highly unstable and cosmopolitan social reality. His novels repeatedly thematise cultural disorientation, migration, and the efforts of establishing a minimum of social and narrative stability in the form of a home. The chapter reads Gurnah’s fiction against a background of Zanzibari history and diaspora and suggests that various forms of “entanglements” paradoxically provide the means to pull the subject out of states of anxiety and alienation into more viable states of being. Vera’s novels engage a powerful Zimbabwean discourse on history, and the psychic and bodily wounds that result from its violent impact on the subject. Set at moments of special and contested historical importance, her novels address the exclusions and silences of this discourse in order both to assess its effects and the possibilities of imagining alternative versions that would allow other modes of subjectivity. These possibilities are manifested, thematically and textually, through an improvisational form of “movement,” geographical, linguistic, and musical. Dabydeen’s fiction investigates the textual dimensions of identity and its connections to larger cultural archives of tropes and languages. Focusing on the constraining yet constitutive impact of various modes of colonial and racial rhetoric, his literary texts display a manipulation of textual elements from these archives that approaches a re-conception of the subject. To describe this manipulation of English and Caribbean sources, thematised and dramatically staged in his fiction, I am using Dabydeen’s own phrase, “creative amnesia.”
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| 10. |
- Schéele, Susanne, et al.
(author)
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Laminin {alpha}1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.
- 2005
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:5, s. 1502-1506
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Journal article (peer-reviewed)abstract
- basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm {alpha}1 chain contains five Lm globular (LG) domains. In vitro, {alpha}1LG1–3 domains bind integrins, and {alpha}1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that {alpha}1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of {alpha}1LG4–5 (also called E3) has not been studied. Mice lacking {alpha}1LG4–5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm {alpha}1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of {alpha}1LG4–5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, {alpha}1LG4–5 provides vital signals for the conversion of stem cells to polarized epithelium.
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